# Optic Stalk-Disc Development and Differentiation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $371,249

## Abstract

Project Summary 
 
This proposal investigates the underlying causes of human ocular diseases using mouse 
models. Proposed experiments will use complex in vivo conditional (cre-­lox) mouse genetics, 
mouse transgenics, histology, immunohistochemistry, confocal microscopy, in situ hybridization, 
mouse embryology, single-­cell NEXTgen sequencing, bioinformatics, BAC recombineering, 
qPCR, and PCR technologies to address basic, mechanistic questions about optic stalk-­disc 
development and astrocyte differentiation.  The Pax2 transcription factor initiates expression in 
all optic vesicle cells, but becomes progressively restricted to only the forming optic disc and 
stalk.  Consistent with its role in other embryonic tissues, we will test a hypothesis that Pax2 
shuts off neural/retinal progenitor gene programs, via global interactions with cell epigenetic 
machinery.  This activity initially restricts ocular cells to an astrocytic progenitor cell (APC) fate, 
regulates their rate of cell division, and initiates glial gene expression profiles.  In Aim 1, we will 
test evolutionarily-­conserved Pax2 noncoding sequences as long-­sought optic disc-­nerve 
enhancer(s) by creating a new Pax2-­Cre driver. This tool will be used to conditionally remove 
Hes1 and assess the consequences to optic stalk development, APC differentiation and mature 
astrocyte functionality.  For Aim 2, we will take advantage of previously characterized Rax-­Cre 
BAC transgenic mouse line, Pax2GFP knock-­in and new Pax2 floxed allele to follow the ocular 
GFP lineages in control and Pax2 conditionally mutant cells.  We will also generate and 
compare the gene expression profiles of Pax2 E11 and E12 heterozygous and homozygous 
mutant eyes.  Here we will use single-­cell RNA sequencing and the growing wealth of publicly 
available information regarding chromatin configurations, and mRNA expression levels during 
the normal development of mouse ocular cells.

## Key facts

- **NIH application ID:** 10415746
- **Project number:** 1R01EY033729-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Nadean L Brown
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $371,249
- **Award type:** 1
- **Project period:** 2022-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10415746

## Citation

> US National Institutes of Health, RePORTER application 10415746, Optic Stalk-Disc Development and Differentiation (1R01EY033729-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10415746. Licensed CC0.

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